1.Platelet membrane biomimetic nanomedicine induces dual glutathione consumption for enhancing cancer radioimmunotherapy.
Xiaopeng LI ; Yang ZHONG ; Pengyuan QI ; Daoming ZHU ; Chenglong SUN ; Nan WEI ; Yang ZHANG ; Zhanggui WANG
Journal of Pharmaceutical Analysis 2024;14(12):100935-100935
Radiotherapy (RT) is one of the most common treatments for cancer. However, intracellular glutathione (GSH) plays a key role in protecting cancer from radiation damage. Herein, we have developed a platelet membrane biomimetic nanomedicine (PMD) that induces double GSH consumption to enhance tumor radioimmunotherapy. This biomimetic nanomedicine consists of an external platelet membrane and internal organic mesoporous silica nanoparticles (MON) loaded with 2-deoxy-D-glucose (2-DG). Thanks to the tumor-targeting ability of the platelet membranes, PMD can target and aggregate to the tumor site, which is internalized by tumor cells. Within tumor cells overexpressing GSH, MON reacts with GSH to degrade and release 2-DG. This step initially depletes the intracellular GSH content. The subsequent release of 2-DG inhibits glycolysis and adenosine triphosphate (ATP) production, ultimately leading to secondary GSH consumption. This nanodrug combines dual GSH depletion, starvation therapy, and RT to promote immunogenic cell death and stimulate the systemic immune response. In the bilateral tumor model in vivo, distal tumor growth was also well suppressed. The proportion of mature dendritic cells (DC) and CD8+ T cells in the mice was increased. This indicates that PMD can promote anti-tumor radioimmunotherapy and has good prospects for clinical application.
2. Prognostic value of pretreatment albumin to globulin ratio in prostate cancer patients treated with maximal androgen blockade
Huafeng ZHANG ; Jia ZHAO ; Daoming XU ; Long XIA
Chinese Journal of Geriatrics 2019;38(10):1153-1157
Objective:
To investigate the prognostic value of pretreatment albumin to globulin ratio(AGR)in prostate cancer(Pca)patients treated with maximal androgen blockade(MAB).
Methods:
Clinical and pathological data of 210 Pca patients who underwent MAB as first-line therapy between January 2013 and June 2018 were retrospectively analyzed.The ages of patients in our cohort ranged from 61 to 90 years, with a mean of(77.0±6.5)years.According to the cut-off point for AGR calculated by the receiver-operating curve analysis, patients were categorized into two groups: the high-AGR group and the low-AGR group.Clinical and pathological features were compared between the groups.Independent factors affecting prognosis were analyzed by using univariate and multivariate analysis.
Results:
The median follow-up duration was 44.0 months.Of the 210 patients, 99 cases had castration resistance, 100 patients(47.6%)had disease progression and 67 patients(31.8%)died.The cut-off point for AGR calculated by the receiver-operating curve analysis was 1.56.There were 103 cases in the low-AGR group(AGR<1.56)and 107 cases in the high-AGR group(AGR≥1.56). Univariate analysis revealed that the progression-free survival(PFS), cancer-specific survival(CSS)and overall survival(OS)were lower in the low-AGR group than in the high-AGR group[1.773(1.298~2.442), 1.948(1.220~3.213), 1.965(1.217~2.996), all
3.Clinical analysis of Xingnaojing injection combined with gastroenteric fluid replacement in the treatment of hyperosmolar nonketotic diabetic coma
Journal of Navy Medicine 2017;38(5):408-410,417
Objective To investigate the clinical effect of Xingnaojing injection combined with gastroenteric fluid replacement in the treatment of hyperosmolar nonketotic diabetic coma ( HNDC) .Methods In accordance with different treatment methods , 150 HNDC patients who received medical care in the Neurological and Endocrinological Department of the hospital from April 2015 to April 2017 were divided into 3 groups, i.e.the conventional treatment group , the gastroenteric fluid replacement group and the Xingnaojing injection combined with gastroenteric fluid replacement group (or the combination group ), each consisting of 50 patients.Blood bio-chemical indexes and changes in plasma osmotic pressure were detected in the patients of the 3 groups, both before therapy and at hour 24 and hour 48 after therapy, and the therapeutic efficacy , rate of complications and mortality were also closely observed .Results To-tal effective rates of the gastroenteric fluid replacement group and the combination group were significantly higher than that of the con -ventional treatment group(P<0.01).As compared with that of the gastroenteric fluid replacement group , total effective rate of the combination group was also significantly higher(P<0.05).The levels of blood glucose, serum sodium, blood urea nitrogen and plasma osmotic pressure at hour 24 and hour 48 after treatment were all lower than those before treatment (P<0.01).The levels of blood glu-cose, serum sodium, blood urea nitrogen and plasma osmotic pressure in the patients of the gastroenteric fluid replacement group and the combination group were obviously lower than those of the conventional group at corresponding time points (P<0.05), and the a-bove-mentioned levels of the combination group were lower than those of the gastroenteric fluid replacement group (P<0.05).The rate of adverse reactions and mortality of the combination group were obviously lower than those of the gastroenteric fluid replacement group and the conventional group (P<0.05 or P<0.01).Conclusion The therapeutic efficacy of Xingnaojing injection combined with gas-troenteric fluid replacement in the treatment of hyperosmolar nonketotic diabetic coma is superior to those of the conventional fluid re -placement and single gastroenteric fluid replacement treatment , and this treatment method is simple and safe , which is worth further clinical extension .
4.Observation on the clinical value of intervention therapy in the treatment of 49 cases of ICVD
Jie WEI ; Changming GENG ; Daoming WEI ; Jieyi LIU
Journal of Navy Medicine 2016;37(1):47-49
Objective To investigate and analyze the near and long-term therapeutic effects of intervention therapy on ische-mic cerebrovascular disease ( ICVD) patients and its clinical value .Methods Clinical data of 110 ICVD patients who received treat-ment at our hospital from April 2012 to May 2015 were retrospectively analyzed .In accordance with different regimens , the patients were divided into two groups:the simple drug treatment group (or the control group) (61 cases) and the intervention therapy group (or the observation group) (49 cases).Then, general medical data, comprehensive evaluation scores before and after the treatment and NIHSS scores were compared between the 2 groups.Results There was no statistical significance in the pathologically affected vessels before therapy, when comparisons were made between the two groups (P>0.05).However, statistical significance could all be seen in the damaged vessels, after 3 days and 12 months of treatment (P>0.05).In addition, statistical significance could also be noted in the therapeutic effect of the damaged vessels at day 3 and month 12, when compared with that before treatment(P<0.01).There was no statistical significance in NIHSS scores detected before therapy for the cerebral infarction patients of the groups (P>0.05).Statisti-cal significance could all be noticed in NIHSS scores , after 1, 6 and 12 months of therapy(P <0.01).Conclusion Intervention ther-apy is a safe and effective method for the treatment of ICVD patients , its near and long-term therapeutic effects are superior to those of the pure drug therapy .
5.Effects of the dominant negative form of protein phosphatase 2A catalytic subunit α driven by alpha-fetoprotein enhancer/phosphoglycerate kinase promoter on hepatoma cell xenografts
Feiran GONG ; Wei LI ; Kai CHEN ; Min TAO ; Daoming LI ; Zekuan XU
Chinese Journal of Hepatobiliary Surgery 2013;19(9):696-700
Objective To investigate the effects of AFP enhancer/pgk promoter driven expression of the dominant negative form of the PP2A catalytic subunit α (DN-PP2Acα) in vivo.Methods The previously constructed AFpg promoter-driven DN-PP2Acα was recombined into an adenovirus,and the expression of PP2Ac was tested using Western blot.Cell growth was tested using the MTT and flat plate clone formation assays.In vivo studies were performed in tumor xenograft models.Results AFpg promoter-driven expression of DN-PP2Acα exerted cytotoxic effects against the AFP-positive human hepatoma cell line HepG2,but did not affect AFP-negative human hepatoma cells (SKHEP-1) or normal human liver cells (L-02).Moreover,AFP enhancer/pgk promoter driven expression of DN-PP2Acα inhibited the growth of AFP-positive HepG2 tumors in nude mice bearing solid tumor xenografts,but did not affect AFP-negative SK-HEP-1 tumors.Conclusion The recombinant AFP enhancer/pgk promoter-driven DN-PP2Acα expression adenovirus presented selective cytotoxicity against AFP-positive hepatoma cells and provides a useful gene therapy strategy to selectively target hepatocellular carcinoma.

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